A jugular venous catheter will be placed under local anaesthesia in lambs 1-7 days of age. Alloxan, 150 mg/kg will be administered. After 24 hours, the blood glucose level will be determined and the lamb anaesthesized with phenobarbital, 20 mg/kg. Following tracheal incubation, the chest will be opened and the animals prepared for measurement of left ventricular performance, coronary blood flow and myocardial O2 and substrate uptake. Contractility will be assessed by measurement of LV dP/dt max, with aortic pressure and flow held constant and cardiac frequency controlled by electrical pacing. Coronary flow will be diverted from the cannulated hemiazyous vein to a jugular vein and measured by timed collections. Simultaneous blood samples will be drawn from the aorta and coronary sinus, and analyzed for O2 content, glucose and free fatty acid (FFA) concentrations, PO2, PCO2, pH and hematocrit values. Extraction and uptake of O2, glucose and FFA will be calculated and compared with simultaneous measurements of LV function. Measurements will be made 15 minutes before, at the time of insulin (80U) administration, and at 30 minute intervals thereafter. At 2 hours a NE dose-respone curve will be obtained. Control lambs will be studied in precisely the same manner, except that saline will replace alloxan. In selected studies, the effects of adrenergic factors will be assessed by the use of beta blocking agents and reserpine. The effects of longer term insulin depletion will be studied in additional lambs given smaller doses of alloxan 2-4 weeks prior to evaluation of cardiac function and metabolism.